Erectile dysfunction: A sentinel marker for cardiovascular disease in primary care
←
→
Page content transcription
If your browser does not render page correctly, please read the page content below
MARTIN M. MINER, MD* LOUIS KURITZKY, MD*
Department of Family Medicine, Brown University Department of Community Health and Family Medicine,
School of Medicine, Providence, RI University of Florida, Gainesville, FL
Swansea Family Practice Group, Swansea, MA
Erectile dysfunction: A sentinel marker for
cardiovascular disease in primary care
■ ABSTRACT ■ PREVALENCE AND SOCIAL IMPLICATIONS
Erectile dysfunction (ED) is a common, age-related Reported prevalence has varied
disorder that diminishes quality of life for affected Reviews of the epidemiologic literature on ED suggest
men and their partners. While most ED is now recog- that about 5% to 35% of men have moderate to
nized as organic in origin, both organic and psycho- severe ED, with differences in prevalence stemming
genic causes often conspire to reduce sexual func- from differences in how ED is defined, the age groups
tion in men with ED. Vasculopathy has come to be studied, concomitant medical conditions, and
methodologic differences.3
recognized as the most common cause of ED, which
One of the largest prevalence studies to date, the
has elevated ED’s importance in the primary care multinational Men’s Attitudes to Life Events and
setting as a sentinel to underlying cardiovascular Sexuality (MALES) study, involved interviews of
disease. Identification of cardiovascular risk factors 27,839 men aged 20 to 75 years from the general pop-
should be a routine part of the evaluation for ED ulation in Europe and North and South America, and
and is as important as taking the patient’s sexual, found a 16% overall prevalence of ED and a 22%
medication, and psychosocial histories. Involving the prevalence in the United States.4
patient’s partner in evaluation and management is The Massachusetts Male Aging Study was a com-
often valuable. Treatment with phosphodiesterase munity-based, random-sample survey of 1,290 men
type 5 inhibitors is effective in restoring sexual func- aged 40 to 70 years who were asked to categorize their
tion for most men with ED, but patients and their erectile function as either complete impotence, mod-
partners should be encouraged to make an informed erate impotence, minimal impotence, or no impo-
tence.5 A full 52% of the men reported some degree
choice from among all available treatment options.
of ED, with 25% reporting moderate ED and 10%
reporting complete ED.5 These findings underscore
■ DEFINITION OF THE CONDITION how much the reported prevalence of ED depends on
how the condition is defined.
Erectile dysfunction (ED) is “the consistent or recur-
rent inability of a man to attain and/or maintain a An age-dependent disorder
penile erection sufficient for sexual performance,” Both of the above studies demonstrated that ED is an
according to the First International Consultation on age-dependent disorder. In the Massachusetts Male
Erectile Dysfunction, convened by the World Aging Study, between the ages of 40 and 70 years, the
Health Organization in 1999.1 This definition closely probability of complete impotence tripled (from 5.1% to
mirrors that of a National Institutes of Health con- 15%) and the probability of moderate impotence dou-
sensus development panel, which further specified bled (from 17% to 34%), while the probability of mini-
“recurrent inability” as being 3 months or greater in mal impotence remained constant at 17%.5 Among
duration.2 men at the upper end of the age range (70 years), only
32% reported that they were free of ED.5 In the MALES
study, though the overall prevalence of ED was lower
* Dr. Kuritzky reported that he has received honoraria from Pfizer, Eli Lilly, because of how ED was defined, the prevalence again
ICOS, Bayer, and GlaxoSmithKline for teaching/speaking or consulting. increased with age, rising steadily from 8% among men
Dr. Miner reported that he has received a research grant from Auxilium
Pharmaceuticals and consulting fees from GlaxoSmithKline/Schering-Plough in their 20s to 37% among men in their 70s.4
and Sanofi-Aventis for consulting and serving on speakers’ bureaus. The prevalence of ED, or at least of diagnosed and
S30 CLEVELAND CLINIC JOURNAL OF MEDICINE VOLUME 74 • SUPPLEMENT 3 MAY 2007
Downloaded from www.ccjm.org on November 4, 2021. For personal use only. All other uses require permission.MINER AND KURITZKY
recognized ED, is only expected to increase as endocrine factors and on coordination of the parasym-
improved awareness of the condition leads to a greater pathetic and sympathetic nervous systems.10 With sexual
likelihood that physicians will diagnose it and as the stimulation, parasympathetic activity enhances produc-
group of men at risk grows with the aging of the over- tion of cyclic guanosine monophosphate (cGMP),
all US population. resulting in cavernosal smooth muscle relaxation and
Despite reduced quality of life, most cases go untreated an influx of blood into the penis. This filling of the
Sexual function is a high priority for men and their penis produces expansion of the sinusoidal spaces, com-
partners throughout the life span. Loss of sexual har- pressing venous channels and thereby preventing out-
mony reduces the quality of life of men and their part- flow of blood to allow maintenance of a rigid erection.
ners. Early references cite the issue of performance What goes wrong in ED
anxiety and the shift from lovemaking as a sensual ED results from physical (eg, hormonal, neurologic,
experience to one fraught with anxiety; during subse- vascular, or cavernosal) and/or psychological factors
quent attempts at lovemaking, the ability to acquire that disrupt this sequence. Physical causes of disruption
or maintain an erection dominates the sexual experi- include injury, surgery (eg, prostatectomy, procto-
ence.6,7 Interventional trials indicate that restoration colectomy, vascular surgery), and comorbid conditions
of sexual function improves quality of life both for that affect the vasculature and peripheral nervous sys-
men with ED and for their partners.8 tem (eg, diabetes, hypertension, dyslipidemia, periph-
Unfortunately, up to 70% of men with ED go eral arterial disease, obesity, coronary artery disease).
untreated.3 Many men fail to seek treatment because The role of the vascular system is noteworthy, as it is
they mistakenly believe that ED is a normal part of now generally accepted that most ED results from a
aging. Others admit to embarrassment as the reason vascular disturbance of the endothelium. This impair-
for not seeking treatment or discussing ED with their ment in endothelial function typically results from vas-
physicians. In the MALES study, only 58% of men culopathy, such as in dyslipidemia, hyperglycemia,
with self-reported ED sought medical attention for it.4 smoking toxicity, or hypertension. ED arises from a
A sentinel for cardiovascular disease combination of endothelial disturbance and abnormal
A final—and perhaps most significant—social implica- smooth muscle function with blood flow abnormalities
tion of ED is its increasingly recognized status as an early that lead to difficulties developing or maintaining an
marker of vascular disease, as detailed in the following erection. The same factors that lead to oxidative stress
section. Knowledge that a man has ED should prompt and impair endothelial function in the cardiovascular
thorough scrutiny for traditional cardiovascular risk fac- and peripheral vascular beds play a fundamental role in
tors, since early detection may allow reduction of car- the underlying pathogenesis and progression of ED 11
diovascular disease risk or attenuation of existing disease. (see “ED as a marker of vascular disease” below).
Other contributors to ED include neurogenic fac-
■ PATHOGENESIS tors (eg, diabetes, multiple sclerosis), endocrinologic
ED is a neurovascular phenomenon modulated by factors (eg, hypogonadism, hyperprolactinemia), or
hormonal and local biochemical interactions as well psychogenic factors (eg, excessive sympathetic tone
as by biomechanical mechanisms that influence due to performance anxiety), although the etiology is
neurovascular control.9 less clear in these settings.
In the past, ED was believed to be largely psy- A key insight: The role of nitric oxide
chogenic in origin. Today we recognize that most ED is Prior to the past decade, ED was managed by urolo-
organic in origin, although it is equally acknowledged gists, who generally used intracavernosal injection
that men with organic ED often will suffer significant therapy, vacuum pumps, and penile prostheses as their
psychological stress as a result. Once a man fails in his primary tools. Most men with ED did not seek treat-
sexual performance, he usually will have fear or anxiety ment because of the relative unpalatability of these
that the failure will recur. For this reason it often is choices. It was not simply the advent of oral medica-
oversimplistic to categorize ED as “solely organic” or tions that changed the tide; after all, oral yohimbine
“solely psychogenic”; rather, both components can had been available for several decades. Rather, it took
contribute to reduce sexual function in men with ED. the availability of highly effective oral therapy, in the
Normal erectile function form of phosphodiesterase type 5 (PDE-5) inhibitors,
Penile erection is a hemodynamic process that depends to spur large numbers of men with ED to seek restora-
on the successful interaction of neurologic and tion of sexual function.
CLEVELAND CLINIC JOURNAL OF MEDICINE VOLUME 74 • SUPPLEMENT 3 MAY 2007 S31
Downloaded from www.ccjm.org on November 4, 2021. For personal use only. All other uses require permission.ERECTILE DYSFUNCTION
Critical in the development of highly effective oral of data from the Prostate Cancer Prevention Trial
therapy was elucidation of the role of nitric oxide. demonstrated that men with ED have a significantly
Nitric oxide is fundamental to vasodilation, including greater chance of experiencing a cardiovascular event
dilation of the corpora cavernosa. Insight into the rela- (angina, myocardial infarction, cerebrovascular acci-
tionship between nitric oxide production and success- dent, transient ischemic attack, congestive heart fail-
ful vasorelaxation, together with the serendipitous dis- ure, or cardiac arrhythmia) than men without ED.20
covery that PDE-5 inhibition enhances accumulation This study, which enrolled men aged 55 years or older,
and survival of penile cGMP, enabled recognition of also showed that incident ED (the first report of ED of
the critical nature of penile endothelial function. any grade) may predict the risk of later cardiovascular
Although cGMP may be generated via the nitrergic events as effectively as does smoking, dyslipidemia, or
nervous system or as a result of endothelial metabolism, a family history of myocardial infarction.20
defects in either pathway may lead to functional Other studies have pointed to similar conclusions.
deficits in erection. PDE-5 inhibitors, by preventing A prospective angiographic study of men with ED of
cGMP breakdown, were shown to enhance erectile vascular origin showed that 19% had angiographically
function. The advent of these medications, together documented silent coronary artery disease.13
with their ease of use, brought ED management into Separately, Ponholzer et al found that men with mod-
the primary care arena and brought the era of urologist- erate to severe ED had a 65% increased risk for devel-
centered management to an end. oping coronary artery disease within 10 years, based
on Framingham risk profile assessment, compared
ED as a marker of vascular disease with men without ED;16 analysis of the actual event
Vasculopathy is now recognized as the most common data from this study is still awaited.
cause of organic ED, and ED is considered one of the ED and sexual function may be a useful tool for strat-
earliest manifestations of vascular disease. Indeed, ifying risk in men with known or suspected coronary
vasculopathy should be suspected in a man presenting artery disease. A recent prospective study of men
with ED until proven otherwise. referred for nuclear stress testing found that those with
Men with traditional risk factors for cardiovascular ED exhibited more severe coronary artery disease and
disease—hypertension, smoking, dyslipidemia, dia- left ventricular dysfunction and had shorter exercise
betes, overweight, sedentary lifestyle—are now recog- times and lower Duke treadmill scores compared with
nized to also be at risk for ED. These risk factors are men without ED.21
more common in men with ED than in those without These findings all support the results of studies link-
ED.12–17 For instance, in a survey of 2,869 men aged 20 ing ED with prevalent and incident cardiovascular dis-
to 80 years, hypertension, hyperlipidemia, and dia- ease.11,22–24 The literature consistently demonstrates that
betes each increased the risk of ED twofold to three- signs of penile endothelial dysfunction (ie, ED) are
fold.16 The individual components of the metabolic often evident in patients with existing coronary artery
syndrome—central obesity, high blood pressure, ele- disease, cerebrovascular disease, or peripheral arterial
vated triglyceride level, low high-density lipoprotein disease that has not yet manifested.25 The presence of
cholesterol level, and glucose intolerance—are also ED should be a wake-up call to clinicians that vascu-
risk factors for ED. lopathy in nonpenile beds is likely. Given that more
Endothelial dysfunction is believed to be the com- than 50% of men do not have warning signs of coronary
mon initiator of ED and other atherosclerotic dis- artery disease prior to their first cardiovascular event,20
eases.18 Men with ED but no other clinical cardiovas- ED could be a sentinel marker for the presence of occult
cular disease were found to have reduced flow-medi- vascular disease in asymptomatic men. Thus, ED is
ated vasodilation in the brachial artery in response to clearly a potential marker of a man’s vascular health.
sublingual nitroglycerin, indicating endothelial dys-
function and abnormal smooth muscle relaxation.11 ■ EVALUATION
Evidence is accumulating that endothelial dysfunc- The examination and history should be directed to
tion is an early functional change thought to precede identify recognized contributors to ED: diabetes,
atherosclerotic changes in the cerebrovascular, coro- hypertension, dyslipidemia, cigarette smoking, hypo-
nary, and peripheral circulations. gonadism, cardiovascular disease, medications known
In addition to its commonality of risk factors with to cause ED, past surgical procedures, and psychoso-
cardiovascular disease, ED is a marker of potential or cial contributors such as relationship problems or
occult cardiovascular disease.19,20 A secondary analysis depression. In the primary care setting, this can often
S32 CLEVELAND CLINIC JOURNAL OF MEDICINE VOLUME 74 • SUPPLEMENT 3 MAY 2007
Downloaded from www.ccjm.org on November 4, 2021. For personal use only. All other uses require permission.MINER AND KURITZKY
be streamlined if the patient’s history is known. If not evaluation and management process is wise.30 An
known, a pertinent sexual, medical, and psychosocial Italian study reported that 40% of men with ED had
history can be performed efficiently within the time never discussed the problem with their partner.31
constraints of the typical office visit. Because most men with ED are in midlife or
Sexual history beyond, their similarly aged partners may be suffering
ED can develop at any age, but because its prevalence burdens that make the resumption of harmonious sex-
rises steeply at about age 40 years,5 it is wise to particu- ual intimacy more difficult (eg, menopausal lubrica-
larly inquire about sexual health for men at this age and tion deficits, changes in libido, pain syndromes, inter-
beyond. Such inquiry is appropriate at any age, however, rupted sleep). This further argues for incorporating
especially as it can also address safe sexual practices.26 the partner into discussion of treatment plans.
Because some recognized vasculopathies (diabetes, Moreover, partner involvement may enhance the
uncontrolled hypertension, marked dyslipidemia) chance of treatment success. Women whose partners
accelerate the process of endothelial dysfunction, men were treated for ED have been found to experience
who have such disorders merit inquiry about their sexual improvements in sexual arousal, orgasm, and sexual
function, regardless of age. Indeed, the case has been satisfaction,32 and quality-of-life scores of both
made that inquiry into sexual health should be one of patients and their partners have been shown to
the “vital signs of lifestyle” asked of all patients.27 improve following treatment of ED.33
Disorders during the desire phase of the sexual cycle
(libido) can be elicited by asking if the patient still Medication history
feels desire or has sexual thoughts or fantasies.28 Taking a medication history can uncover a drug that
Difficulty in the desire phase may be a sign of hypo- may be responsible for ED, such as a narcotic anal-
gonadism, relationship difficulties, medication- gesic, a benzodiazepine, or another central nervous
induced ED, or depression. system depressant prescribed for chronic pain. In cur-
Difficulties with arousal or erection can be elicited rent practice, the medications most associated with
by asking if the patient has trouble obtaining and sexual dysfunction are hydrochlorothiazide and selec-
maintaining an erection.28 If the patient reports erectile tive serotonin reuptake inhibitors, although the latter
difficulty, inquire about onset, frequency, and any rela- are more commonly associated with orgasmic dys-
tionship to medical treatments or stressful events. The function than with ED.
line of inquiry should then include questions about spe- A comparative trial assessing sexual function in
cific times and circumstances in which the patient gets hypertensive men receiving either an angiotensin
erections (eg, in the morning, with masturbation, dur- receptor blocker or a beta-blocker showed a higher
ing sexual activity with his partner) and how firm these incidence of ED in men taking the beta-blocker.34
erections are. For example, ED in a patient who has Although this finding might seem to be an indict-
strong morning erections but poor erections with his ment of beta-blockers, it could equally well reflect a
partner is likely to have a psychogenic component. salutary effect of angiotensin receptor blockers.
Standardized questionnaires can assist in the diag- Substantial controversy surrounds the potential role
nosis of ED and facilitate discussion of sexual health, of beta-blockers in causing sexual dysfunction.
especially when the patient is reluctant to initiate such Because sexual dysfunction has been reported in data
discussion. The Sexual Health Inventory for Men is a sets for dozens of medications, it is worth reviewing the
five-item survey with four questions that pertain to the patient’s medication history to identify any clear tem-
ability to attain and maintain an erection and the fre- poral relationships between a particular drug and sexual
quency of erections sufficient for intercourse.29 The dysfunction. If such a relationship exists, it is reasonable
results of this and any other questionnaire on sexual to substitute an alternate medication or, when possible,
health must be interpreted in the context of the attempt a drug holiday or medication cessation.
patient’s psychosocial factors, including desire and Physical examination
the opportunity to have sexual relations. Although The traditional physical examination includes blood
this and other questionnaires can help identify the pressure measurement and a genital examination to
presence of ED, they do not elucidate its etiology. assess testicular size. Testicles that are small (< 2 cm)
Involve the partner or appear atrophic to palpation should prompt confir-
Whenever possible and when the patient is in agree- mation of testosterone status. Other physical findings
ment, including the patient’s sexual partner in the associated with ED include penile plaques (Peyronie
CLEVELAND CLINIC JOURNAL OF MEDICINE VOLUME 74 • SUPPLEMENT 3 MAY 2007 S33
Downloaded from www.ccjm.org on November 4, 2021. For personal use only. All other uses require permission.ERECTILE DYSFUNCTION
TABLE 1
Profile of pharmacologic therapies for erectile dysfunction41,42
Recommended interval between Duration
Therapy Standard dose dosing and intercourse of action
Oral phosphodiesterase type 5 inhibitors
Sildenafil 50–100 mg 1 hr ⭓ 4 hr
Tadalafil 10–20 mg 0.5–12 hr 36 hr
Vardenafil 10–20 mg 0.5–1 hr < 5 hr
Intracavernosal injection
Alprostadil* 5–40 μg 10–30 min 1–4 hr
Intraurethral suppository
Alprostadil pellet* 0.5–1 mg 5–10 min 1 hr
*The only medication approved by the US Food and Drug Administration for this method of administration.
disease), which may cause painful or deviated erec- foundation for ED therapy, although data from con-
tions and thus lead to sexual dysfunction, and an trolled trials on the effects of individual lifestyle
enlarged prostate, which can be identified by digital changes on ED are limited.
rectal examination. Some data are starting to emerge, however. A
A vascular examination, including palpation of the recent study of obese men with ED (but without dia-
femoral vessels and listening for bruits, may be appro- betes, hypertension, or hyperlipidemia) found that
priate, and neurologic examination may be helpful. reducing calorie intake and increasing physical activ-
ity was associated with improved sexual function in
Laboratory tests about one third of obese men.38 An Iranian study of
Because ED is a sentinel for vasculopathy in other smoking cessation in men with ED found that ED sta-
compartments, laboratory testing should seek cardio- tus improved at 1-year follow-up in at least 25% of
vascular risk factors. Basic initial laboratory tests for men who stopped smoking during the study period
suspected ED are fasting serum glucose level and a compared with 0% of continuing smokers.39 The ben-
lipid panel, especially low-density and high-density efit was greatest in younger men and in those with less
lipoprotein cholesterol. Testosterone levels should be severe ED prior to smoking cessation.39
considered in those men with ED who also have Data on incident ED from a cohort study led to
metabolic syndrome, diabetes mellitus, or decreased somewhat different conclusions: among men without
libido, given that low testosterone may be associated ED at baseline, midlife adoption of lifestyle changes to
with these conditions.9,35,36 Morning serum total tes- reverse the effects of smoking, obesity, and alcohol
tosterone should also be considered as an additional consumption may be too late to reduce the risk of ED,
laboratory test in patients whose ED is refractory to although increased physical activity may reduce ED
initial therapy, as should prolactin, luteinizing hor- risk even if adopted in midlife.40
mone (if testosterone is < 200 ng/dL or the patient is
< 50 years old), and thyroid-stimulating hormone. Oral drug therapy (PDE-5 inhibitors)
Some experts suggest urinalysis to detect potential The goal of therapy for ED is restoration of sexual
renal disease or infection, although these are rarely function. There are several types of therapy options,
associated with ED.37 A complete blood count and and the choice among them should be an informed
metabolic panel may identify a potential hematologic decision by the patient and his partner based on the
disorder or renal or liver disease. efficacy, risks, benefits, and costs of each option. Most
patients and their partners will, given all available
■ TREATMENT choices, elect an oral agent—specifically, a PDE-5
Lifestyle changes inhibitor—but this is not to say that the other options
Given the important vascular component of ED, detailed below (intracavernosal injection therapy,
behavioral modifications such as weight loss, increased vaccum constriction devices, intraurethral supposito-
exercise, and smoking cessation are an appropriate ries) may not have a role.
S34 CLEVELAND CLINIC JOURNAL OF MEDICINE VOLUME 74 • SUPPLEMENT 3 MAY 2007
Downloaded from www.ccjm.org on November 4, 2021. For personal use only. All other uses require permission.MINER AND KURITZKY
The three PDE-5 inhibitors available in the United other PDE-5 inhibitors), patients should be made
States—sildenafil, tadalafil, and vardenafil—are simi- aware that any PDE-5 inhibitor should be tried six to
larly effective in improving and maintaining erections eight different times at full dose before it is deemed
suitable for intercourse, though they differ somewhat ineffective. Because patient misadventure and misad-
in pharmacokinetics and dosing (Table 1).41,42 Clinical ministration may occur despite the best instructions, it
trials demonstrate that PDE-5 inhibitor therapy suc- is wise to ask patients to return after whatever interval
cessfully enables almost three quarters of men with ED is required for this six- to eight-dose trial period. For
to achieve an erection adequate to complete inter- most couples, this will be 3 to 4 weeks, but the inter-
course,37 although results are highly dependent on the val should be tailored to the couple’s preference.
patient population studied—eg, diabetic men and
post-prostatectomy patients are less likely to respond.33 Intracavernosal injection therapy
All PDE-5 inhibitors are approximately equally effi- Another approach to ED involves injection of
cacious, and there are no large head-to-head random- alprostadil, a prostaglandin, into the corpora caver-
ized trials to suggest that one agent has meaningfully nosa (Table 1). Despite the development of intracav-
superior efficacy over another.43 In preference trials, ernosal injection products that are fully appropriate
some patients express distinct preference for one PDE- to primary care settings, most primary care providers
5 inhibitor over another, but this too is hard to pre- have not been trained in their use.45 Additionally,
dict. Most couples at midlife and beyond have sexual most patients will prefer methods of treatment other
activity no more than once within 24 hours, and any than injection. Nonetheless, an occasional patient
of the available PDE-5 inhibitors can be effective in may prefer intracavernosal injection therapy for per-
this setting. The only area where these agents appear sonal reasons, and it is an option for patients who are
to differ is in half-life, as tadalafil has a longer half-life intolerant of or unresponsive to PDE-5 inhibitors or
than the other two PDE-5 inhibitors, which translates in whom those drugs are contraindicated.
to a longer duration of action (Table 1).41,42 Some cli-
nicians allow patients to try all three PDE-5 inhibitors Vacuum constriction devices
to determine their personal preference. Vacuum constriction devices (VCDs) consist of a
All PDE-5 inhibitors require sexual stimulation to cylinder that is placed over the penis and a pump that
achieve an erection. creates a vacuum within the cylinder. The negative
The side effect profiles of the three PDE-5 pressure generated within the cylinder causes blood to
inhibitors are very similar, and all three agents are flow into the corpora cavernosa, facilitating erection.
contraindicated in patients taking long-acting Once an erection is achieved, a constrictor ring is
nitrates or nitroglycerin.43 placed around the base of the penis so that blood is
Because absorption of sildenafil may be meaning- retained within the corpora cavernosa.
fully reduced by food, it is best not to take it in close Prior to the availability of PDE-5 inhibitors, VCDs
proximity to meals, especially high-fat meals. Var- were used successfully in many men with ED. The
denafil shows some diminution in absorption after a device can be viewed as cumbersome, however, and
high-fat meal, but not enough to impair efficacy. VCD-induced erections can differ from “sponta-
Absorption of tadalafil is not affected by food.41 neous” erections in color and/or temperature as a
Patients should be instructed that near-maximal result of the constriction ring. Still, VCDs have
concentrations are reached about 1 hour after admin- essentially no serious side effects, can work in ED of
istration of sildenafil and vardenafil and about 2 hours multiple etiologies,46 and are economical; for these
after administration of tadalafil.41 Some patients reasons a VCD may be a viable option for couples
achieve a therapeutic response within 15 minutes, but who are attracted by its simplicity, avoidance of sys-
since most do not experience such rapid onset, it is temic medications, or cost.45,47
wise to suggest the more conservative timing at first.44 Long-term continuation rates with VCDs vary
Over time, patients will become more and more widely (35% to 81%),48–50 but in our experience,
familiar with the time to onset of action. dropout rates are inversely related to the thoroughness
Patients should be instructed about the timing of of initial instruction in VCD application and use.
administration, the need for sexual stimulation, the Frequent reasons for VCD discontinuation include
expected success rate, and the fact that the first few inadequate penile rigidity, the “unnaturalness” of the
doses may not be successful. Based on data from erection produced, pain from the pressure of the con-
sildenafil trials (similar data are not available for the striction ring, difficulty in use, and failure to ejaculate.51
CLEVELAND CLINIC JOURNAL OF MEDICINE VOLUME 74 • SUPPLEMENT 3 MAY 2007 S35
Downloaded from www.ccjm.org on November 4, 2021. For personal use only. All other uses require permission.ERECTILE DYSFUNCTION
Intraurethral alprostadil suppositories Peyronie disease is present, or when there is a lack of
Like intracavernosal injection therapy, another treat- treatment success.28 As noted, referral to a sex thera-
ment approach employs the prostaglandin alprostadil pist should be considered when relationship problems
but applies it topically as a urethral suppository using appear to be the cause of ED or an important contrib-
an applicator (Table 1). The penis is then massaged utor to it.
to dissolve the alprostadil pellet, after which venous
flow delivers alprostadil to the corpora cavernosa, ■ REFERENCES
where it will induce erection.52 The patient generally 1. Jardin A, Wagner G, Khoury S, et al. Recommendations of the 1st
needs to be standing when the pellet is inserted and International Consultation on Erectile Dysfunction. Cosponsored
by the World Health Organization, International Consultation on
walk around for about 10 minutes before the erection Urological Diseases, and Société Internationale d’Urologie. Paris,
will develop. Pellet insertion should be preceded by France: July 1–3, 1999; Geneva, Switzerland: World Health
urination to moisten the urethra and ease insertion. Organization; 1999:709–726.
2. NIH Consensus Development Panel on Impotence. Impotence
The patient should be instructed on the proper tech- [NIH Consensus Conference]. JAMA 1993; 270:83–90.
nique for inserting the suppository, which requires 3. Kubin M, Wagner G, Fugl-Meyer AR. Epidemiology of erectile
that the initial insertion be done in the primary care dysfunction. Int J Impot Res 2003; 15:63–71.
4. Rosen RC, Fisher WA, Eardley I, Niederberger C, Nadel A, Sand
provider’s office.41,43 M. The multinational Men’s Attitudes to Life Events and Sexuality
Because of lower levels of efficacy (30% success (MALES) study: I. Prevalence of erectile dysfunction and related
rate),53 local adverse effects, and relatively high cost, health concerns in the general population. Curr Med Res Opin
2004; 20:607–617.
intraurethral suppositories do not enjoy as widespread 5. Feldman HA, Goldstein I, Hatzichristou DG, Krane RJ, McKinlay
popularity as other forms of therapy for ED. JB. Impotence and its medical and psychosocial correlates: results of
the Massachusetts Male Aging Study. J Urol 1994; 151:54–61.
Treatment for psychogenic factors 6. Reynolds CF 3rd, Frank E, Thase ME, et al. Assessment of sexual
function in depressed, impotent, and healthy men: factor analysis of a
Cognitive-behavioral interventions and relationship Brief Sexual Function Questionnaire for men. Psychiatry Res 1988;
counseling are among the treatment approaches for psy- 24:231–250.
chogenic ED. These interventions are often combined 7. Tiefer L, Schuetz-Mueller D. Psychological issues in diagnosis and
treatment of erectile disorders. Urol Clin North Am 1995;
with pharmacologic therapy. Primary care clinicians 22:767–773.
should consider referral to a sexual therapist if psy- 8. Dunn ME. Restoration of couple’s intimacy and relationship vital to
chogenic factors are the cause of, or contribute to, ED. reestablishing erectile function. J Am Osteopath Assoc 2004; 104(3
Suppl 4):S6–S10.
9. Burnett AL. Erectile dysfunction. J Urol 2006; 175(3 Pt 2):S25–S31.
■ APPROPRIATE FOLLOW-UP 10. Rosen RC, Kostis JB. Overview of phosphodiesterase 5 inhibition
in erectile dysfunction. Am J Cardiol 2003; 92(9A):9M–18M.
After treatment is prescribed, follow-up is important to 11. Kaiser DR, Billups K, Mason C, Wetterling R, Lundberg JL, Bank AJ.
evaluate treatment success, monitor for adverse effects, Impaired brachial artery endothelium-dependent and -independent
and adjust the dose or type of treatment as necessary. vasodilation in men with erectile dysfunction and no other clinical
cardiovascular disease. J Am Coll Cardiol 2004; 43:179–184.
There is no evidence-based guidance for the follow-up 12. Roth A, Kalter-Leibovici O, Kerbis Y, et al. Prevalence and risk
schedule, which should be tailored to the couple’s pref- factors for erectile dysfunction in men with diabetes, hypertension,
erence and usual frequency of sexual activity. or both diseases: a community survey among 1,412 Israeli men. Clin
Cardiol 2003; 26:25–30.
Generally, follow-up should be sufficiently soon so that 13. Vlachopoulos C, Rokkas K, Ioakeimidis N, et al. Prevalence of
obstacles to successful treatment can be promptly asymptomatic coronary artery disease in men with vasculogenic
addressed, and should be at least periodic thereafter. erectile dysfunction: a prospective angiographic study. Eur Urol
2005; 48:996–1002.
14. Nikoobakht M, Nasseh H, Pourkasmaee M. The relationship
■ WHEN TO REFER between lipid profile and erectile dysfunction. Int J Impot Res 2005;
17:523–526.
The role of the primary care clinician in ED manage- 15. Ponholzer A, Temml C, Obermayr R, Wehrberger C, Madersbacher S.
ment will depend on personal preference. It may vary Is erectile dysfunction an indicator for increased risk of coronary
from simple identification of ED and subsequent heart disease and stroke? Eur Urol 2005; 48:512–518.
16. Ponholzer A, Temml C, Mock K, Marszalek M, Obermayr R,
referral, to the use of oral medications, VCDs, intra- Madersbacher S. Prevalence and risk factors for erectile dysfunction
cavernosal injection, and uretheral suppositories. in 2,869 men using a validated questionnaire. Eur Urol 2005;
Despite the typically supportive relationship between 47:80–85.
17. Fung MM, Bettencourt R, Barrett-Connor E. Heart disease risk
primary care clinicians and their patients, some factors predict erectile dysfunction 25 years later: the Rancho
patients may prefer the relative anonymity of a con- Bernardo Study. J Am Coll Cardiol 2004; 43:1405–1411.
sultant for a condition as intimate as ED. 18. Shabsigh R. Correlation between erectile dysfunction and metabol-
ic syndrome. In: Sadovsky R, ed. Heart of the Matter: Erectile
Referral to a urologist is appropriate for complex Dysfunction as an Early Sign of Vasculopathy. Livingston, NJ:
cases of ED, when an anatomic problem such as CogniMed Inc.; 2005:14–21.
S36 CLEVELAND CLINIC JOURNAL OF MEDICINE VOLUME 74 • SUPPLEMENT 3 MAY 2007
Downloaded from www.ccjm.org on November 4, 2021. For personal use only. All other uses require permission.MINER AND KURITZKY
19. Jackson G, Rosen RC, Kloner RA, Kostis JB. The second sex hormone-binding globulin predict the metabolic syndrome and
Princeton consensus on sexual dysfunction and cardiac risk: new diabetes in middle-aged men. Diabetes Care 2004; 27:1036–1041.
guidelines for sexual medicine. J Sex Med 2006; 3:28–36. 37. Kuritzky L, Miner M. Erectile dysfunction assessment and man-
20. Thompson IM, Tangen CM, Goodman PJ, Probstfield JL, Moinpour agement in primary care practice. In: Broderick GA, ed. Oral
CM, Coltman CA. Erectile dysfunction and subsequent cardiovascu- Pharmacotherapy for Male Sexual Dysfunction: A Guide to Clinical
lar disease. JAMA 2005; 294:2996–3002. Management. Totowa, NJ: Humana Press; 2005:149–184.
21. Min JK, Williams KA, Okwuosa TM, Bell GW, Panutich MS, Ward 38. Esposito K, Giugliano F, Di Palo C, et al. Effect of lifestyle changes
RP. Prediction of coronary heart disease by erectile dysfunction in men on erectile dysfunction in obese men: a randomized controlled trial.
referred for nuclear stress testing. Arch Intern Med 2006; 166:201–206. JAMA 2004; 291:2978–2984.
22. Bocchio M, Desideri G, Scarpelli P, et al. Endothelial cell activa- 39. Pourmand G, Alidaee MR, Rasuli S, Maleki A, Mehrsai A. Do
tion in men with erectile dysfunction without cardiovascular risk cigarette smokers with erectile dysfunction benefit from stopping?: a
factors and overt vascular damage. J Urol 2004; 171:1601–1604. prospective study. BJU Int 2004; 94:1310–1313.
23. Gazzaruso C, Giordanetti S, De Amici E, et al. Relationship 40. Derby CA, Mohr BA, Goldstein I, Feldman HA, Johannes CB,
between erectile dysfunction and silent myocardial ischemia in McKinlay JB. Modifiable risk factors and erectile dysfunction: can
apparently uncomplicated type 2 diabetic patients. Circulation lifestyle changes modify risk? Urology 2000; 56:302–306.
2004; 110:22–26. 41. 2007 Physicians’ Desk Reference. Montvale, NJ: Thomson
24. Billups KL. Endothelial dysfunction as a common link between Healthcare; 2006.
erectile dysfunction and cardiovascular disease. Curr Sex Health 42. Drug Facts and Comparisons. St. Louis, MO: Wolters Kluwer; April
Rep 2004; 1:137–141. 2006.
25. Kirby M, Jackson G, Simonsen U. Endothelial dysfunction links erec- 43. Montague DK, Jarow JP, Broderick GA, et al; Erectile Dysfunc-
tile dysfunction to heart disease. Int J Clin Pract 2005; 59:225–229. tion Guideline Update Panel. Chapter 1: The management of erec-
26. Billups KL, Bank AJ, Padma-Nathan H, Katz S, Williams R. tile dysfunction: an AUA update. J Urol 2005; 174:230–239.
Erectile dysfunction is a marker for cardiovascular disease: results of 44. Shabsigh R, Burnett AL, Eardley I, et al. Time from dosing to sex-
the Minority Health Institute Expert Advisory Panel. J Sex Med ual intercourse attempts in men taking tadalafil in clinical trials.
2005; 2:40–52. BJU Int 2005; 96:857–863.
27. Kuritzky L. Taking a male sexual history. Curr Sex Health Rep 45. Kuritzky L, Ahmed O, Kosch S. Management of impotence in pri-
2006; 3:61–65. mary care. Compr Ther 1998; 24:137–146.
28. Sadovsky R, Dunn M, Grobe BM. Erectile dysfunction: the pri- 46. Lewis RW, Witherington R. External vacuum therapy for erectile
mary care practitioner’s view. Am J Manag Care 1999; 5:333–341. dysfunction: use and results. World J Urol 1997; 15:78–82.
29. Cappelleri JC, Rosen RC. The Sexual Health Inventory for Men 47. Sadeghi-Nejad H, Seftel AD. Vacuum devices and penile implants.
(SHIM): a 5-year review of research and clinical experience. Int J [chapter 15]. In: Seftel AD, ed. Male and Female Sexual Dys-
Impot Res 2005; 17:307–319. function. Philadelphia, PA: Mosby; 2004.
30. Kuritzky L. Counseling the patient with erectile dysfunction: a pri- 48. Dutta TC, Eid JF. Vacuum constriction devices for erectile dys-
mary care physician perspective. J Am Osteopath Assoc 2002; function: a long-term, prospective study of patients with mild, mod-
102(12 Suppl 4):S7–S11. erate, and severe dysfunction. Urology 1999; 54:891–893.
31. Mirone V, Gentile V, Zizzo G, et al. Did men with erectile dys- 49. Cookson MS, Nadig PW. Long-term results with vacuum constric-
function discuss their condition with partner and physicians? A sur- tion device. J Urol 1993; 149:290–294.
vey of men attending a free call information service. Int J Impot Res 50. Turner LA, Althof SE, Levine SB, et al. Treating erectile dysfunc-
2002; 14:256–258. tion with external vacuum devices: impact upon sexual, psycholog-
32. Cayan S, Bozlu M, Canpolat B, Akbay E. The assessment of sexual ical and marital functioning. J Urol 1990; 144:79–82.
functions in women with male partners complaining of erectile dys- 51. Hatzimouratidis K, Hatzichristou DG. A comparative review of
function: does treatment of male sexual dysfunction improve female the options for treatment of erectile dysfunction: which treatment
partner’s sexual functions? J Sex Marital Ther 2004; 30:333–341. for which patient? Drugs 2005; 65:1621–1650.
33. McMahon CG, Samali R, Johnson H. Efficacy, safety and patient 52. Hellstrom WJ, Bennett AH, Gesundheit N, et al. A double-blind,
acceptance of sildenafil citrate as treatment for erectile dysfunction. placebo-controlled evaluation of the erectile response to
J Urol 2000; 164:1192–1196. transurethral alprostadil. Urology 1996; 48:851–856.
34. Fogari R, Zoppi A, Poletti L, et al. Sexual activity in hypertensive 53. Brock G. MUSE and intracavernosal therapies [chapter 14]. In:
men treated with valsartan or carvedilol: a crossover study. Am J Seftel AD, ed. Male and Female Sexual Dysfunction. Philadelphia,
Hypertens 2001; 14:27–31. PA: Mosby; 2004.
35. Dhindsa S, Prabhakar S, Sethi M, et al. Frequent occurrence of
hypogonadotropic hypogonadism in type 2 diabetes. J Clin
Endocrinol Metab 2004; 89:5462–5468. Address: Martin M. Miner, MD, Swansea Family Practice Group, 479
36. Laaksonen DE, Niskanen L, Punnonen K, et al. Testosterone and Swansea Mall Drive, Swansea, MA 02777; martin_miner@brown.edu.
CLEVELAND CLINIC JOURNAL OF MEDICINE VOLUME 74 • SUPPLEMENT 3 MAY 2007 S37
Downloaded from www.ccjm.org on November 4, 2021. For personal use only. All other uses require permission.You can also read
